Prostatic Neoplasms: Kamidono S

Kamidono S, Ohshima S, Hirao Y, Suzuki K, Arai Y, Fujimoto H, Egawa S, Akaza H, Hara I, Hinotsu S, Kakehi Y, Hasegawa T, Anonymous00384. · No affiliation provided · Int J Urol. · Pubmed #18184166 No free full text.

This publication has no abstract.

Li H, Sugimura K, Boku M, Kaji Y, Tachibana M, Kamidono S. · Department of Radiology, Kobe University, School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. · Eur Radiol. · Pubmed #16440233 No free full text.

Abstract: We report MR imaging characteristics of a prostatic urethral polyp in a 35-year-old man. Traditionally, the methods of diagnosis include computed tomography, transrectal sonography, voiding cysto-urethrography, intravenous pyelography, urethroscopy, and cystoscopy. To our knowledge, MR findings have not been previously described. In this case, MR imaging clearly demonstrated a polypoid tumor located in the prostatic urethra with a stalk connected to the bladder neck. A pathological study revealed the polyp consisted of a fibrovascular core covered with a double layered, prostatic-type epithelium.

Gotoh A, Shirakawa T, Wada Y, Hinata N, Terao S, Hara I, Arakawa S, Kamidono S, Okada H, Takenaka A, Fujisawa M. · The International Center for Medical Research, Kobe University School of Medicine. · Hinyokika Kiyo. · Pubmed #15773357 No free full text.

Abstract: We selected bone-metastatic prostate cancer as the target form of recurrent prostate cancer and developed a suicide-gene therapy based on an adenovirus vector with an organ-specific osteocalcin promoter. Related clinical studies have already been conducted in the United States at the University of Virginia, where results so far have established the safety of this therapy. In the present paper, in addition to presenting the results of these gene-therapy studies from the basic research to the clinical stage, we discuss the clinical studies begun by our group in August 2003. In the 21st century, therapeutic systems in use are undergoing major changes. Gene therapy is likely to become an important therapeutic option in recurrent prostate cancer. In terms of theory and technology however, this form of treatment is still at a very immature stage of development. We look forward to evolution in this field to provide an established treatment for recurrent prostate cancer and are committed to actively continuing with the development of gene therapy through translational research.

Shirakawa T, Gotoh A, Wada Y, Kamidono S, Ko SC, Kao C, Gardner TA, Chung LW. · Department of Urology, Kobe University School of Medicine, Kobe, Japan. · Mol Urol. · Pubmed #12006246 No free full text.

Abstract: Delivery of therapeutic toxic genes to and their expression in tumor cells through the use of tissue-specific promoters could decrease their toxic effect on neighboring normal cells when virus-mediated gene delivery results in their infection. We have demonstrated the utility of two prostate cancer-specific promoters, long PSA and osteocalcin, for tissue-specific toxic gene therapy for prostate cancer. The two promoters were highly active in both androgen-dependent and androgen-independent prostate cancer cells. We also introduce the Phase I trial of osteocalcin promoter-based toxic gene therapy for bone metastases of prostate cancer, which is in progress at the University of Virginia.

Miyake H, Hara I, Kamidono S, Gleave ME. · The Prostate Center, Vancouver General Hospital, Vancouver, Canada. · Int J Urol. · Pubmed #11442654 No free full text.

Abstract: Progression to androgen-independence remains the main obstacle to improving survival for patients with advanced prostate cancer. In this review, findings are summarized that have recently been demonstrated to establish novel therapeutic strategy targeting several genes playing functionally important roles after androgen withdrawal and during androgen-independent progression. The authors initially characterized changes in gene expression after androgen withdrawal in the androgen-dependent Shionogi and LNCaP tumor models using cDNA arrays. Based on these results, they focused on genes highly upregulated after androgen ablation (i.e. bcl-2, bcl-xL, TR.PM-2, IGFBP-5), which have anti-apoptotic or mitogenic activities, and thereby confer a resistance to androgen withdrawal as well as cytotoxic chemotherapy. The authors further demonstrated the efficacy of an antisense oligodeoxynucleotide (ODN) strategy for patients with advanced prostate cancer through the inhibition of target gene expression, resulting in a delay in the progression to androgen-independence by enhancing apoptotic cell death induced by androgen ablation and chemotherapy. The authors also showed the effectiveness of combined antisense ODN therapy and cytotoxic chemotherapy by achieving additive or synergistic effects. These findings provide a basic significance for the design of clinical studies using antisense ODN either alone or in combination with chemotherapeutic agents in patients with advanced prostate cancer.

Shirakawa T, Terao S, Hinata N, Tanaka K, Takenaka A, Hara I, Sugimura K, Matsuo M, Hamada K, Fuji K, Okegawa T, Higashihara E, Gardner TA, Kao C, Chung LW, Kamidono S, Fujisawa M, Gotoh A. · International Center for Medical Research and Treatment, Kobe University School of Medicine, Kobe 650-0017, Japan. · Hum Gene Ther. · Pubmed #18021019 No free full text.

Abstract: We evaluated the long-term safety and efficacy of Ad-OC-TK (recombinant adenoviral vector carrying an osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) gene therapy for hormone-refractory prostate cancer. Ad-OC-TK/VAL therapy is the first in vivo adenovirus-mediated gene therapy to be used to treat metastatic prostate cancer, including bone metastasis. Six patients were enrolled in this trial, and two doses of Ad-OC-TK (2.5 x 10(9) or 2.5 x 10(10) plaque-forming units) were injected into locally recurrent tumor or bone metastasis on day 1 and day 8. Patients were also given VAL (3 g/day) for 21 days. Safety and efficacy were evaluated for at least 8 months in each patient. All patients tolerated this therapy with no serious adverse events. One prostate-specific antigen (PSA) response (from 318.3 to 4.9 ng/ml) was observed with a time to PSA progression (TTP) of 12 months. Docetaxel (30 mg/m2 per week) and estramustine (560 mg/day) combination chemotherapy (DE) was given to three docetaxel-naive patients on PSA failure after gene therapy. All three patients had a PSA response to DE therapy with 21, 7, and 4 months of TTP. These results suggest that additional trials are warranted.

Hinata N, Shirakawa T, Terao S, Goda K, Tanaka K, Yamada Y, Hara I, Kamidono S, Fujisawa M, Gotoh A. · Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. · Int J Urol. · Pubmed #16834676 No free full text.

Abstract: There is no effective therapy for hormone-refractory prostate cancer and a novel therapeutic modality, such as a gene therapy, should be actively pursued. Previously, Gardner and Chung conducted a phase I clinical trial of Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) for the treatment of hormone-refractory prostate cancer at the University of Virginia. We report on our ongoing phase I/II clinical trial of Ad-OC-TK plus VAL for the treatment of advanced prostate cancer at the Kobe University Hospital, Japan.

Hara I, Kawabata G, Miyake H, Hara S, Fujisawa M, Okada H, Arakawa S, Kamidono S. · Department of Urology, Kobe University School of Medicine, Kobe, Japan. · Int J Urol. · Pubmed #12534908 No free full text.

Abstract: OBJECTIVES: The objective of this study was to present the clinical outcomes of 26 patients who underwent laparoscopic radical prostatectomy at our institution. METHODS: We performed laparoscopic prostatectomy on patients who were clinical stage T1 or T2. The mean age was 70 years old (range: 52-76). The mean level of pre-treatment prostate-specific antigen (PSA) was 8.7 ng/mL (range: 3.3-45). The Gleason score of the needle biopsy was < 7 in 21 patients and > or = 7 in five patients. Clinical stage was T1c in 17 patients, T2a in 6 patients and T2b in 3 patients. Operative techniques followed those of the French groups. Five trocars were introduced into the peritoneal cavity. The vas deferens and seminal vesicles were dissected to reach the posterior wall of the prostate and the retroperitoneal space was dissected around the urinary bladder. Incision of endopelvic fascia and dorsal vein complex (DVC) ligation were performed. The bladder neck and prostate were divided, then the distal urethra was cut. The lateral pedicles of the prostate were cut and the entire prostate was removed. Vesico-urethral anastomosis was performed at eight points. RESULTS: Mean operation time was 7 h 30 min. Mean bleeding volume (including urine volume) was 850 mL (range: 32-3135). All patients underwent autologous blood transfusion. Only one patient required further blood transfusion. Gleason scores of resected specimens were < 7 in 10 patients, and > or = 7 in 16 patients. Pathological stage was T0 in 1 patient, T2a in 6 patients, T2b in 13 patients, T3a in 5 patients and T3b in 1 patient. The PSA value was undetectable in all patients one month after surgery. Ten patients who survived for 6 months after surgery had complete urinary continence without a pad. In 7 of the 12 patients who were potent before surgery, neurovascular bundles were preserved, and 5 of them (71%) achieved complete or incomplete erection 3 months after surgery. However, only one patient (14%) could have sexual intercourse. CONCLUSION: Although longer follow-up is necessary to evaluate this surgical technique, laparoscopic prostatectomy seems to be a reasonable option in the treatment of organ-confined prostate cancer.

Hara I, Miyake H, Yamada Y, Takechi Y, Hara S, Gotoh A, Fujisawa M, Okada H, Arakawa S, Soejima T, Sugimura K, Kamidono S. · Department of Urology, Kobe University School of Medicine, Japan. · Int J Urol. · Pubmed #12269247 No free full text.

Abstract: BACKGROUND: It is unclear whether positive interactions between radiation and androgen withdrawal for patients with locally advanced prostate cancer is synergistic or additive. The present study aimed to clarify the significance of neoadjuvant androgen ablation prior to external radiotherapy in a human prostate LNCaP tumor model and in patients with locally advanced prostate cancer. METHODS: Comparisons were made between the effect of castration prior to radiation on the growth of subcutaneous LNCaP tumors implanted into male nude mice and their serum prostate-specific antigen (PSA) levels, and the results of castration or radiation alone. Twenty-nine patients with histologically proven and locally advanced adenocarcinoma of the prostate were treated with luteinizing hormone-releasing hormone analog at least 3 months before, during, and after external radiation therapy with a total dose of 70 Gy. The toxicity and response to this therapy were evaluated. RESULTS: Treatment combining castration and radiation resulted in synergistic inhibition of LNCaP tumor growth and a significant delay in the emergence of androgen-independent recurrence as opposed to either treatment alone. The external radiotherapy was completed in 28 patients (96.6%), resulting in a reduction of serum PSA levels in all 28 patients to below 1.0 ng/mL. All patients were alive after a mean follow-up period of 34 months (range 11-53) with a 3-year PSA relapse-free survival rate of 83.7%. Among several factors examined, only the Gleason score was significantly associated with PSA relapse-free survival in univariate analysis, but not in multivariate analysis. Thirteen of 28 patients (46%) and 7 of 28 (25%) also showed at least one form of gastrointestinal or genitourinary toxicity, respectively. Of these patients, 8 with gastrointestinal toxicities, and 1 with genitourinary toxicity, experienced acute complications higher than grade 3. CONCLUSION: The experimental findings objectively suggested the use of neoadjuvant androgen withdrawal prior to radiation therapy. Although our clinical experience is preliminary, combined androgen ablation and radiation therapy may also be effective in controlling locally advanced prostate cancer, with tolerable side-effects.

Fujisawa M, Higuchi A, Gotoh A, Matsui T, Hara I, Gohji K, Okada H, Arakawa S, Kamidono S. · Department of Urology, Kobe University School of Medicine, Japan. · Int J Urol. · Pubmed #10226811 No free full text.

Abstract: PURPOSE: In order to evaluate precise anastomosis using a Foley catheter, complications following radical retropubic prostatectomy were examined. METHODS: Twenty-one patients underwent radical retropubic prostatectomy. Precise vesicourethral anastomosis was performed, visualizing the urethral stump by raising up the urogenital diaphragm using a Foley catheter. Complications, such as prolonged urinary extravasation and temporary urinary retention, were checked when the catheter was removed. Incontinence was evaluated both within 6 weeks and more than 6 weeks after operation. Anastomotic and urethral strictures were also checked during follow up. RESULTS: The follow-up period ranged from 4 to 47 months (mean (+/- SD) 22.0 +/- 12.1 months). Eighteen of 21 patients (85.7%) achieved continence after the operation. However, two patients still had stress incontinence and one patient had mild incontinence. Neither prolonged urinary extravasation nor temporally urinary retention were observed. Anastomotic and urethral stricture were not experienced during follow up. CONCLUSIONS: Precise anastomosis using a Foley catheter is technically easy and useful, even for relatively inexperienced urologists, to perform. Patients can often achieve continence following this procedure.

Shigemura K, Shirakawa T, Wada Y, Kamidono S, Fujisawa M, Gotoh A. · Division of Urology, Department of Organ Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. · Urology. · Pubmed #16360450 No free full text.

Abstract: OBJECTIVES: To investigate the effects of the selective cyclooxygenase-2 (COX-2) inhibitor etodolac on prostate cancer cell lines in vitro and in vivo and on E-cadherin expression in prostate cancer cells. METHODS: We evaluated the cytotoxicity of etodolac on the three prostate cancer cell lines LNCaP, C4-2, and PC-3. We also performed quantitative real-time polymerase chain reaction to measure the mRNA expression of COX-2, Bcl-2, and E-cadherin in these cell lines after etodolac treatment. In addition, we investigated the in vivo antitumor effects of etodolac on a human prostate cancer xenograft model. RESULTS: Etodolac exhibited significant antitumor effect in vivo and in vitro. The cytotoxicity of etodolac in LNCaP and C4-2 was markedly increased at a dose of 1000 nM in a time-dependent and dose-dependent manner. In the in vivo tumor growth study, the etodolac-treated mice exhibited more significant cytotoxicity than the phosphate-buffered saline-treated mice. Expression of E-cadherin after etodolac treatment tended to increase and that of Bcl-2 to decrease, but the expression of COX-2 had no definite tendency. CONCLUSIONS: The COX-2 inhibitor etodolac exhibited an antitumor effect on prostate cancer cell lines in vitro and in vivo, and it might be useful for the treatment of hormone-resistant prostate cancer.

Muramaki M, Miyake H, Hara I, Kamidono S. · The Prostate Centre, Jack Bell Research Centre, Vancouver, British Columbia V6H 3Z6, Canada. · Int J Oncol. · Pubmed #15703816 No free full text.

Abstract: TNP-470, a potent inhibitor of angiogenesis, was reported to synergistically enhance the antitumor effects of cytotoxic agents. The objective of this study was to evaluate the effectiveness of combined treatment with TNP-470 and docetaxel both in vitro and in vivo using androgen-independent human prostate cancer PC-3 cells. The in vitro growth-inhibitory and apoptotic effects of docetaxel and/or TNP-470 on PC-3 cells were assessed using MTT and TUNEL assays. The combined effect of docetaxel and TNP-470 therapy after subcutaneous and orthotopic injection of PC-3 cells into athymic nude mice was evaluated. In vivo effects of this combined regimen on PC-3 tumors were analyzed by the TUNEL assay and immunohistochemical staining of CD31 to quantify microvessel density (MVD). Combined treatment with TNP-470 and docetaxel synergistically inhibited PC-3 cell growth in vitro through the enhanced induction of apoptotic cell death compared with treatment with either agent alone, a result explained, at least in part, by the down-regulation as well as phosphorylation of potential anti-apoptotic genes, Bcl-2 and Bcl-XL. Combined treatment with TNP-470 and docetaxel synergistically suppressed subcutaneous PC-3 tumor growth compared with treatment with either agent alone. Furthermore, this combined regimen significantly inhibited orthotopic PC-3 tumor growth and reduced the incidence of lymph node metastasis. Immunohistochemical analysis of the subcutaneous tumor after each treatment demonstrated that administration of docetaxel as well as TNP-470 significantly induced apoptotic cell death; in contrast, a significant reduction in MVD was observed only after TNP-470. These findings suggest that docetaxel and TNP-470 act synergistically to inhibit PC-3 tumor growth and metastasis, by enhancing apoptosis and suppressing angiogenesis.

Yao A, Harada M, Matsueda S, Ishihara Y, Shomura H, Takao Y, Noguchi M, Matsuoka K, Hara I, Kamidono S, Itoh K. · Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan. · Prostate. · Pubmed #15389794 No free full text.

Abstract: BACKGROUND: Parathyroid hormone-related protein (PTHrP) is produced by cancer cells and has been suggested to be responsible for malignancy-associated hypercalcemia and osteolysis after bone metatsases. Therefore, PTHrP is a promising target in the treatment of metastatic prostate cancer. METHODS: Seven PTHrP-derived peptides were prepared based on the HLA-A2 binding motif. These peptide candidates were screened by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs), and their ability to be recognized by immunoglobulin G (IgG). RESULTS: Both the PTHrP59-67 and PTHrP42-51 peptides were found to efficiently induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. These CTLs showed HLA-A2-restricted cytotoxicity toward prostate cancer cells. IgG reactive to the PTHrP42-51 peptide was frequently detected in prostate cancer patients. CONCLUSIONS: These results indicate that these two new PTHrP peptides will be useful in the peptide-based immunotherapy of HLA-A2+ prostate cancer patients, especially those with bone metastases.

Hara I, Murakami M, Kagawa K, Sugimura K, Kamidono S, Hishikawa Y, Abe M. · Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. · Am J Clin Oncol. · Pubmed #15289722 No free full text.

Abstract: A study was conducted to evaluate the use of proton beam therapy for the treatment of organ-confined prostate cancer. This is a preliminary assessment of treatment-related morbidity and tumor response. Sixteen patients with T1-T2b prostate cancer underwent proton beam therapy. Acute and late toxicity was scored according to the National Cancer Institute Common Toxicity Criteria Grading System (version 2.0, April 1999) and to the Radiation Therapy Oncology Group grading system, respectively. Local control was assessed using magnetic resonance imaging (MRI) and prostate-specific antigen (PSA) values. Although skin toxicity and bladder irritability were commonly observed, none of the patients developed grade III or IV toxicity. Of 9 patients in whom the primary lesion was detected by MRI, partial response and no change (NC) was observed in 6 (66.7%) and 3 (33.3%) patients, respectively. Four patients presented normal PSA value before treatment due to the previous endocrine therapy. However, the other 12 patients with elevated PSA value before treatment showed complete response. No patients showed PSA failure within the median follow-up period of 11.9 months. Although longer follow-up is necessary, minimum toxicity and good short-term clinical responses were observed following proton beam therapy in T1-T2 prostate cancer patients.

Shirakawa T, Hamada K, Zhang Z, Okada H, Tagawa M, Kamidono S, Kawabata M, Gotoh A. · Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. · Clin Cancer Res. · Pubmed #15240520 links to  free full text

Abstract: PURPOSE: Cyclooxygenase-2 (Cox-2), an enzyme that catalyzes the synthesis of prostaglandins, is overexpressed in a variety of premalignant and malignant conditions, including urinary bladder cancer. In the present study, we examined the feasibility of using Cox-2 promoter-based replication-selective adenovirus for targeting bladder cancer cells that express Cox-2 transcriptional activity. EXPERIMENTAL DESIGN: A series of human cancer cell lines, including three bladder cancer cell lines (KK47, T24, and 5637), were evaluated for their Cox-2 and CAR (the Coxsackievirus and adenovirus receptor) mRNA expression levels by quantitative real-time PCR. AdE3-cox2-327, a replication-selective adenovirus in which the expression of E1a is controlled by the Cox-2 promoter, was generated, and its tissue-specific activity was tested in vitro and in vivo. RESULTS: Three bladder cancer cell lines express higher levels of Cox-2 mRNA than does the human prostate cancer cell line PC3, the primary cultured human benign prostatic fibroblast, PF cells, and the human colon cancer cell line Colo320. Relatively higher expression of CAR mRNA was detected in the KK47, 5637, respectively, and Colo320 than in the T24, PC-3, and PF cells. In vitro assays revealed significant growth suppression of both Cox-2- and CAR-expressing bladder cancer cells KK47 and 5637 in comparison with the other cells that lack Cox-2 expression and/or CAR expression. CONCLUSIONS: The present study demonstrated both specificity and efficacy of AdE3-cox2-327, a selectively replicated adenovirus, toward the Cox-2-expressing bladder cancer cells in vitro and in vivo. We also found that CAR expression in the target cancer cells is an important factor for the efficacy of selectively replicated adenovirus-based gene therapy.

Yao A, Harada M, Matsueda S, Ishihara Y, Shomura H, Noguchi M, Matsuoka K, Hara I, Kamidono S, Itoh K. · Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan. · Br J Cancer. · Pubmed #15199397 links to  free full text

Abstract: Parathyroid hormone-related protein (PTHrP) is a key factor in the development of bone metastases, which are a major barrier in treating prostate cancer patients. In this study, we attempted to identify PTHrP-derived peptides immunogenic in human histocompatibility leukocyte antigen (HLA)-A24(+) prostate cancer patients. Among four different PTHrP peptides carrying the HLA-A24 binding motif, both the PTHrP(36-44) and PTHrP(102-111) peptides efficiently induced peptide-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) prostate cancer patients. Peptide-stimulated PBMCs showed cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. Experiments using antibodies and cold inhibition targets confirmed that their cytotoxicity was dependent on PTHrP peptide-specific and CD8(+) T cells. Immunoglobulin G reactive to the PTHrP(102-111) or PTHrP(110-119) peptide was frequently detected in the plasma of prostate cancer patients, suggesting that the PTHrP(102-111) peptide is able to elicit cellular and humoral immune responses in cancer patients. These results indicate that the PTHrP could be a promising target molecule for specific immunotherapy of HLA-A24(+) prostate cancer patients with metastases.

Hara I, Yao A, Muramaki M, Hikosaka S, Yamada Y, Kawabata G, Kamidono S. · Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. · Int J Urol. · Pubmed #15028107 No free full text.

Abstract: Bacillus Calmette-Guerin (BCG) instillation therapy is now a standard therapy for high-risk superficial bladder cancer patients. Although the complete response rate is approximately 70%, extra-vesical progression is sometimes observed. In particular, those patients who present a positive urinary cytology even after complete response from bladder lesion should be thoroughly examined. We present two cases of stromal invasion of the prostate after complete remission by BCG therapy of carcinoma in situ of the ureter and bladder found by transrectal prostate biopsy.

Li H, Sugimura K, Boku M, Kaji Y, Tachibana M, Kamidono S. · Department of Radiology, Kobe University, School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. · Eur Radiol. · Pubmed #15018173 No free full text.

Abstract: We report MR imaging characteristics of a prostatic urethral polyp in a 35-year-old man. Traditionally, the methods of diagnosis include computed tomography, transrectal sonography, voiding cystourethrography, intravenous pyelography, urethroscopy, and cystoscopy. To our knowledge, MR findings have not been previously described. In this case, MR imaging clearly demonstrated a polypoid tumor located in the prostatic urethra with a stalk connected to the bladder neck. A pathological study revealed the polyp consisted of a fibrovascular core covered with a double layered, prostatic-type epithelium.

Miyake H, Hara I, Kamidono S, Eto H. · Department of Urology, Hyogo Medical Center for Adults, Akashi and Kobe University School of Medicine, Kobe, Japan. · J Urol. · Pubmed #15017214 No free full text.

Abstract: PURPOSE: We evaluated the significance of oxidative DNA damage in patients with prostate cancer based on the measurement of urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and analyzed changes in urinary 8-OHdG before and after initial treatment. MATERIALS AND METHODS: A total of 82 patients with prostate cancer were included in this study. Of these 82 patients 42 underwent radical prostatectomy and the remaining 40 received hormonal therapy as initial treatment. Urinary 8-OHdG and creatinine (Cr), and serum prostate specific antigen (PSA) in these 82 patients were assessed before and 2 months after the initiation of treatment. RESULTS: The ratio of urinary 8-OHdG-to-Cr (8-OHdG/Cr) in patients with prostate cancer was significantly higher than in age matched healthy controls. Only age was significantly associated with 8-OHdG/Cr in prostate cancer cases among several clinicopathological factors, including serum PSA clinical T stage, metastasis and Gleason score. There was no significant difference in urinary 8-OHdG/Cr in 42 patients before and after radical prostatectomy, while urinary 8-OHdG/Cr in 40 patients after hormonal therapy was significantly lower than before hormonal therapy. In addition, changes in PSA after initial treatment were not related to changes in urinary 8-OHdG/Cr in either treatment group. CONCLUSIONS: These findings suggest that oxidative stress may be involved in an early event in prostate cancer development and androgen suppression is capable of decreasing oxidative stress. Accordingly androgen withdrawal therapy combined with antioxidative agents may inhibit the progression of prostate cancer.

Gotoh A, Shirakawa T, Wada Y, Fujisawa M, Okada H, Kamidono S, Hamada K. · International Centre for Medical Research and Department of Urology, Kobe University School of Medicine, Kobe, Japan. · BJU Int. · Pubmed #12887490 No free full text.

Abstract: OBJECTIVE: To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. MATERIALS AND METHODS: The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. RESULTS: Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. CONCLUSIONS: These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.

Okada H, Shirakawa T, Miyake H, Gotoh A, Fujisawa M, Arakawa S, Kamidono S. · The Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. · Prostate. · Pubmed #12772193 No free full text.

Abstract: BACKGROUND: Prostatic small-cell carcinoma is an extremely rare, highly aggressive disease. We established a cell line from this tumor. MATERIALS AND METHODS: Tumor tissue obtained from a 24-year-old Japanese man was used to establish the cell line. Cultured cells and tumors transplanted into nude mice were characterized by histologic, immunohistologic, immunocytologic, and molecular biologic methods. RESULTS: An immortal culture cell line (SO-MI) was successfully established. SO-MI cells adhered weakly to plastic surfaces in vitro, showing a 52- to 72-hr doubling time. SO-MI cells were heterotopically and orthotopically transplantable in nude mice. The cells were immunoreactive for NSE, chromogranin A, and NCAM, but not for ACTH, calcitonin, serotonin, gastrin, insulin, glucagons, LCA, EMA, PAP, PSA, androgen receptor, and p53. SO-MI cells secreted NSE in vitro and in vivo. SO-MI cells at passage 30 contained 50-59 chromosomes with a modal number of 55. PCR suggested that the p53 gene was deleted in SO-MI cells. RT-PCR detected no mRNA encoding androgen receptor in these cells. CONCLUSIONS: SO-MI cells retain the neuroendocrine nature of the original tumor, and should be useful in studying possible etiologies and new treatments.

Hara I, Kawabata G, Miyake H, Nakamura I, Hara S, Okada H, Kamidono S. · Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. · J Urol. · Pubmed #12771715 No free full text.

Abstract: PURPOSE: We compare the quality of life after laparoscopic prostatectomy to that after standard radical prostatectomy. MATERIAL AND METHODS: The quality of life of 52 and 54 patients who underwent laparoscopic and open radical prostatectomy, respectively, was analyzed using the European Organization for the Research and Treatment of Cancer Prostate Cancer quality of life questionnaire for general health related quality of life, International Index of Erectile Function 5 for screening erectile dysfunction and International Continence Society MaleSF questionnaire to evaluate urinary status. These questionnaires were given to patients before and 6 months after surgery. RESULTS: The general health related quality of life survey revealed no significant differences in health before and after laparoscopic and open prostatectomy. However, sexual quality of life was markedly lower after surgery (p <0.01). In addition, the International Index of Erectile Function score was markedly abrogated by surgery (p <0.05) and quality of life due to urinary incontinence was significantly disturbed by surgery (p <0.05). In contrast, quality of life due to voiding dysfunction was impaired before surgery and significantly improved by surgery (p <0.05). Patients were also asked if they would choose the same treatment if suffering from the same disease, with more patients treated laparoscopically choosing the same treatment than those treated with open surgery (p <0.05). CONCLUSIONS: While general health related quality of life was not impaired, sexual quality of life was diminished by surgery. Patients were generally satisfied with postoperative urinary status. Although patients who underwent laparoscopic prostatectomy expressed a more favorable attitude toward surgery, there was no significant difference in quality of life at 6 months after surgery between the 2 groups.

Shirakawa T, Fujisawa M, Gotoh A, Okada H, Arakawa S, Kamidono S. · Division of Urology, Department of Organs Therapeutics, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan · Urology. · Pubmed #12639671 No free full text.

Abstract: Synovial sarcomas primarily occur chiefly in the para-articular regions of the extremities and extremely rarely in the prostatic region. We report a patient with synovial sarcoma of the prostatic fascia. The patient underwent retropubic radical prostatectomy and at 6 months of follow-up, no evidence of another lesion or local recurrence was found.

Miyake H, Hara I, Kamidono S, Gleave ME, Eto H. · Department of Urology, Hyogo Medical Center for Adults, Akashi 673-8558, Japan. · Oncol Rep. · Pubmed #12579291 No free full text.

Abstract: We recently reported the powerful antiapoptotic activity of clusterin against various apoptotic stimuli in prostate cancer model systems; however, the precise mode of clusterin action in target cells remains largely unknown. In the present study, we therefore investigated whether intracellular or extracellular action of clusterin plays a crucial role in cytotoxic chemotherapy-induced apoptosis in androgen-independent human prostate cancer PC3 cells, which express a high level of clusterin. The sensitivity of PC3 cells to paclitaxel was increased by pretreatment with monoclonal antibody (mAb) to clusterin or antisense (AS) oligodeoxynucleotide (ODN) targeting the clusterin gene in a dose-dependent manner at up to 50 microg/ml or 1 microM, respectively. However, clusterin mAb failed to further enhance the sensitivity to paclitaxel of PC3 cells simultaneously treated with 1 microM AS clusterin ODN, whereas AS clusterin ODN further induced the apoptosis of cells treated with 50 microg/ml clusterin mAb. Moreover, the effects of clusterin mAb and AS clusterin ODN on PC3 cells were not reversed by additional treatment with exogenous recombinant clusterin protein. These findings suggest that the sensitivity of PC3 cells to paclitaxel-induced cytotoxicity may be regulated by the intracellular rather than extracellular level of clusterin.

Gotoh A, Shirakawa T, Wada Y, Hinata N, Matsubara S, Hara I, Fujisawa M, Okada H, Arakawa S, Kamidono S. · International Center for Medical Research, Kobe University School of Medicine. · Hinyokika Kiyo. · Pubmed #12512150 No free full text.

Abstract: The substantial advances made in recent years in the molecular biology of malignant urological tumors and the associated progressive analysis of these conditions at a molecular level have spurred research aimed at gene-based treatment. In the field of prostate cancer, while there have been many ground-breaking studies particularly in the United States, none has yet led to a revolutionary treatment for recurrent prostate cancer. Gene-based treatment is being applied seriously in clinical settings, especially in the United States, but so far without significant effect. Many researchers worldwide are devoting energy to the development of effective vectors. By adjusting the promoter, which has the function of directing the vector, we have developed organ-specific vectors for the treatment of prostate cancer. In the present study, which targeted prostate cancer with bone metastasis, we developed a suicide-gene therapy using an adenovirus vector with an organ-specific osteocalcin promoter. Clinical trials of this vector have already been conducted at the University of Virginia in the United States and have so far confirmed the safety of the therapy. In the present paper we present the results of this gene-therapy research from the basic to the clinical phase alongside an outline of related research at our institution. Gene therapy for cancer is now being targeted not only against the primary tumor but systemic cancers including distant metastases; systemic administration of adenovirus vectors with organ-specific promoters may become one of the most promising systemic anti-tumor therapies of the next-generation.